Celiac Disease Associated Conditions
All five conditions listed (b, c, d, and e) are definitively associated with celiac disease and warrant screening, while type II autoimmune pancreatitis (a) is associated with idiopathic pancreatitis more broadly but not specifically type II. 1, 2, 3
Confirmed Associations with Strong Evidence
Dermatitis Herpetiformis (c)
- Dermatitis herpetiformis is explicitly identified as a condition requiring celiac disease screening, representing a cutaneous manifestation of gluten sensitivity with essentially 100% association with celiac disease. 3
- Patients with dermatitis herpetiformis should undergo both serology and upper endoscopy with biopsies to confirm celiac disease. 3
Insulin-Dependent Diabetes Mellitus (Type 1 Diabetes) (d)
- The American Gastroenterological Association position statement explicitly recommends testing for celiac disease in patients with type 1 diabetes mellitus, particularly when symptoms suggesting celiac disease are present. 1, 2
- The prevalence of celiac disease in type 1 diabetes patients ranges from 2-10%, with pooled estimates of 3-8% in children and 2-5% in adults—representing a 5-10 fold increased risk compared to the general population. 1, 2, 3
- This association is explained by shared HLA susceptibility genes (DQ2 and DQ8) and the gene encoding cytotoxic T-lymphocyte-associated antigen-4. 4, 5
- Treatment with a gluten-free diet improves glycemic control in patients with concurrent type 1 diabetes and celiac disease. 4
Sjögren's Syndrome (b)
- The American Gastroenterological Association explicitly identifies Sjögren's syndrome as a condition where celiac disease testing should be selectively considered during medical evaluation, particularly when symptoms compatible with celiac disease are present. 1, 2
- The increased prevalence of Sjögren's syndrome in celiac disease patients is explained by shared HLA susceptibility genes (DQ2 and DQ8). 1, 2
- Selective screening is recommended in Sjögren's syndrome patients presenting with fatigue, diarrhea, weight loss, or anemia. 2
Primary Biliary Cholangitis (e)
- The American Gastroenterological Association explicitly recommends testing for celiac disease in patients with primary biliary cirrhosis, with prevalence ranging from 0% to 6.0% and pooled estimates of 3-7%. 1, 2, 3, 4
- Mandatory screening for celiac disease is recommended in primary biliary cholangitis patients with unexplained symptoms. 2
- A gluten-free diet enhances absorption of medications used to treat associated conditions, including those for osteoporosis and hypothyroidism that may accompany primary biliary cholangitis. 4
Autoimmune Pancreatitis Considerations (a)
- Idiopathic pancreatitis is listed as a condition with high celiac disease prevalence warranting screening. 3
- However, the evidence does not specifically distinguish between type I and type II autoimmune pancreatitis, making option (a) less definitively supported than the other associations. 3
Pathophysiologic Mechanism
- More than 60% of celiac disease-associated susceptibility loci are shared with at least one other autoimmune condition, suggesting common pathogenic mechanisms. 6
- The common genetic background (particularly HLA-DQ2 and DQ8) is the main factor determining the high prevalence of these associations. 5
- Recognition of peptides by HLA molecules, posttranslational modifications required for optimal peptide binding, and immune mechanisms leading to tissue damage are found in celiac disease as well as in these associated autoimmune diseases. 6
Clinical Screening Algorithm
For patients with any of these conditions:
- IgA tissue transglutaminase (tTG-IgA) with total IgA level should be the initial screening test. 2
- If patients are undergoing upper endoscopy for any reason, duodenal biopsies should be performed to rule out celiac disease even without positive serology. 3
- In patients with advanced liver disease (relevant for primary biliary cholangitis), tTG antibodies may be falsely elevated, particularly with older guinea pig-based assays. 2